Preliminary data are presented in this proposal showing that 5-Hydroxytryptamine (5-HT) is a potent agonist (threshold equals ten to the minus tenth power M) at the alpha adrenergic receptors of isolated rabbit ear artery. In contrast, 5-HT has no agonist effect at the alpha receptors of rabbit aorta. In a separate line of investigation plus or minus propranolol, its inactive (plus) isomer and three other propranolol-like compounds were shown to be alpha agonists in isolated ear artery but to have no agonist activity in aorta. The most potent agonist of this series, Labetalol (threshold equals ten to the minus seventh power M), was shown to be an alpha receptor antagonist in aorta. On the basis of these findings it is hypothesized that there are at least two postsynaptic alpha receptors in rabbit blood vessels. The purpose of the proposed study is to test this hypothesis. Blood vessel rings will be mounted for the measurement of isometric tension development and the postsynaptic alpha receptors in these tissues will be differentiated according to the two following classical procedures: (1) Dose-response curves will be obtained for a series of alpha adrenergic agonists and the relative orders of potency among the different blood vessels studied will be compared. (2) The antagonist potencies (pA2) of several reversible competitive antagonists will be determined and compared in these same vessels. Classical agonists (e.g., norepinephrine) and antagonists (e.g., phentolamine) will be used to differentiate the alpha receptors of ear artery and aorta. 5-HT and labetalol (the most potent propranolol-like compound) will be used to identify the distribution, in blood vessels, of those alpha receptors which are sensitive to these compounds. The agonist orders of potency of both 5-HT and propranolol analogs will be determined as will antagonist pA2 values to assess whether or not the alpha receptors which are sensitive to 5-HT and propranolol are of one type. The distribution of serotonergic receptors among blood vessels will also be identified using the highly selective antagonist 2-brom-d-lysergic acid diethylamide. Finally, the alpha agonist potencies of the (minus) and (plus) isomers of the propranolol-like compounds will be determined.